Changes in hemodynamics and respiration in rats with different resistance to acute hypoxia

Effects of acute hypoxia on hemodynamics and respiration were studied in acute experiments on narcotized rats. The animals were divided into groups characterized by high, low-, and medium- resistance to hypoxia by the time of respiration arrest during inhalation of gas mixture containing 3% O₂. Hemodynamic parameters of highly resistant animals were higher than in low-resistant rats throughout the entire hypoxic period. The development of a rare (with prolonged inspiratory phase) respiratory rhythm in highly resistant rats is an adaptive reaction, which allows them longer tolerate hypoxia compared to low-resistant animals. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 24–28, July, 2004     

Behavioral peculiarities and reactions of brain dopaminergic systems in rats with different resistance to acute hypobaric hypoxia

Locomotor activity in the open field test did not correlate with rat resistance to acute hypobaric hypoxia; there was a correlation between this resistance and rat behavior during acute stress. Immobility was characteristic of rats with low and particularly medium resistance to hypoxia; this reaction can be abolished by antidepressants. by contrast, highly resistant rats were mainly hyperactive. The resistance to hypoxia was associated with extreme parameters of dopaminergic neuron functioning. In low-resistant rats locomotor stereotypia was maximal, while perioral stereotypia was the minimal; highly resistant rats were characterized by an opposite pattern, and medium-resistant rats occupied an intermediate position.     

Ultrastructure of synapses in cerebral cortex layer i in rats with low and high resistance to hypoxia

Quantitative analysis of synapses in layer I of the sensorimotor cortex in rats with low resistance to hypoxia revealed pronounced changes in the number of synaptic vesicles docked at the presynaptic membrane in active synaptic zones under conditions of acute hypobaric hypoxia. In high-resistant animals the number of docked synaptic vesicles under these conditions remained unchanged. In was hypothesized that high sensitivity to hypoxia in low-resistant rats is determined by high reactivity of the synaptic transmission system.     

Urine Antipyrine Metabolites in Rats with Different Resistance to Hypoxia Subjected to Cold Stress

We studied antipyrine metabolism in rats with different resistance to hypoxia during adaptation to cold stress. Changes in the concentrations of some antipyrine metabolites at low temperature were associated with individual resistance to hypoxia. In low-resistant rats, antipyrine metabolism was suppressed from day 5 of cold exposure to day 3 of the recovery period. In highly resistant rats, antipyrine metabolism was inhibited on day 3 of cold exposure, but returned to normal on day 3 of the recovery period.     

Changes in hemodynamics and respiration in animals with different resistance to acute hypoxia

We studied the effects of acute hypoxia on hemodynamics and respiration in cats. The animals were divided into high-, low- and medium-resistant to hypoxia by the time of respiratory arrest after breathing with 3% O₂ gas mixture. In high-resistant animals, hemodynamic indices remained at a high level throughout the hypoxic episode, while in low-resistant cats they decreased shortly after the onset of hypoxia. It is suggested that the peculiarities of hemodynamic regulation play an important role in individual resistance to acute hypoxia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 9, pp. 286–290, September, 1999     

Behavioral peculiarities and reactions of brain dopaminergic systems in rats with different resistance to acute hypobaric hypoxia

Locomotor activity in the open field test did not correlate with rat resistance to acute hypobaric hypoxia; there was a correlation between this resistance and rat behavior during acute stress. Immobility was characteristic of rats with low and particularly medium resistance to hypoxia; this reaction can be abolished by antidepressants. By contrast, highly resistant rats were mainly hyperactive. The resistance to hypoxia was associated with extreme parameters of dopaminergic neuron functioning. In low-resistant rats locomotor stereotypia was maximal, while perioral stereotypia was the minimal; highly resistant rats were characterized by an opposite pattern, and medium-resistant rats occupied an intermediate position. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 9, pp. 275–278, September, 2000     

Seasonal variations in rat resistance to hypoxia

Resistance to acute hypoxia was evaluated by the life span after elevation to a simulated altitude of 11,500 m at 13.00-21.00 in different seasons of the same year. The period of investigation was divided into 3 parts: beginning (13.00-15.00), middle (16.00-18.00), and end (19.00-21.00) of the day. Animal life span decreased by the end of the day (the decrease was more pronounced in summer and autumn) and by the end of the year, i. e. in autumn (more pronounced in the middle and end of the day). The life span was longer in the middle of the day in spring in low- and medium-resistant rats and by the end of the year in medium-resistant rats (at the beginning of the day). Fluctuations in the life span during the day and year were more expressed in low- and medium-resistant rats. Differences in the life span of highly and low-resistant rats were the most pronounced in winter.     

Antihypoxic effects of derivative on the EEG power spectra in rats with different susceptibility to oxygen deficiency

The succinate-containing hydroxypyridine derivative yancarb increases both the altitude tolerated by rats and their survival time at a high altitude, particularly in rats with low resistance to hypobaric hypoxia; it also prevents both phasic changes in the EEG characteristic of hypobaric hypoxia and hemispheric asymmetry and paroxysmal activity in the brain of highly resistant rats in the 5000–10,000 m range and in rats with low resistance in the 5000–11,000 m range. Antihypoxic effects of this substance are more pronounced in low-resistance rats and in the left hemisphere of both high- and low-resistant animals; in altitude range of 10,000–13,000 m these effects are weaker or absent. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 7, pp. 57–62, July, 1997     

Effect of Transitory Ischemia on Liver Lysosomal Apparatus in Rats with Different Resistance to Hypoxia

We studied the state of lysosomal apparatus and pro- and antioxidant activity in the liver of rats with different resistance to hypoxia during postischemic recovery. Under normal conditions the lysosomal apparatus did not differ in highly and low resistant animals. During ischemia and reperfusion the damage to hepatic lysosomal membranes in rats highly resistant to hypoxia was less pronounced than in low resistant animals. These differences also concerned labilization of lysosomes during exposure to damaging factors (hypotonia and Triton X-100). The rats highly resistant to hypoxia differed from low resistant animals by higher stability of lysosomal membranes, lower prooxidant activity (malonic dialdehyde content), and higher tissue concentration of -tocopherol during reperfusion.     

Specific Response of the Organism and Blood Leukocytes in Rats of Different Genetic Strains to Hypoxia

By the open-field behavior, August rats were more resistant to acute hypoxia than Wistar rats. Hypoxic activation of the immune system was more pronounced in August rats. As differentiated from Wistar rats, the stress-limiting NO system in August rats was not suppressed during hypoxia. The effectiveness and resistance of this system to hypoxia were higher in August rats. Behavioral changes in Wistar rats under hypoxic conditions were accompanied by activation of HSP32 synthesis in blood leukocytes. This protein serves as an indicator of oxidative stress (i.e. adverse factor in hypoxia). August rats were more resistant to behavioral disturbances in hypoxia than Wistar rats. HSP32 synthesis in leukocytes from August rats was not impaired under hypoxic conditions. Our results indicate that variations in HSP32 synthesis in peripheral blood leukocytes can be considered as a matter of for resistance to acute hypoxia. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 10, pp. 391–394, October, 2008     

Effect of acute hypoxia on resistance to hypoxia in rats

The resistance of rats to hypoxia was measured by survival time after exposure to high-altitude (11.5 km) hypoxia. The first exposure to acute hypoxia caused phasic changes in the survival time: short-term in high-resistant rats (about 24 h) and long-term in moderate- and lowresistant rats (38–39 days) starting from 1 h and 6–7 days after the first exposure, respectively. Adaptive reactions were more pronounced in low- and moderate-resistant rats, while disadaptation was typical of high-resistant animals. In all rats, the adaptive effect dominated until days 22–23. Throughout the testing, the initial type of resistance was retained in 79% of high-resistant rats, in 41% of low-resistant and in 33% of moderate-resistant rats, i. e., the initially homogenous groups formed after the first exposure in accordance with the type of resistance became mixed, which reduced the intergroup differences. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 6, pp. 625–628, June, 1999     

Effects of Preconditioning on the Resistance to Acute Hypobaric Hypoxia and Their Correction with Selective Antagonists of Nicotinic Receptors

Hypobaric hypoxic preconditioning increased the resistance of low resistant and highly resistant rats to acute hypobaric hypoxia at a critical height. Intergroup differences in the resistance of rats to acute hypobaric hypoxia were not observed after hypobaric hypoxia and one variational series with a wide range of resistance (4.5-24.5 min) appeared. Methyllycaconitine, an antagonist of subtype α₇ nicotinic cholinergic receptors, abolished the influence of hypobaric hypoxia on low resistant rats, but had no effect on highly resistant animals. Mecamylamine, a preferential antagonist of subtype α₄β₂ and α₃-containing cholinergic receptors, did not modulate the effect of hypobaric hypoxia. By contrast, hypobaric hypoxia abolished the effect of mecamylamine on the resistance of rats that were not trained under conditions of hypobaric hypoxia (low resistant and highly resistant animals with low sensitivity to hypobaric hypoxia). We conclude that the same effect of hypobaric hypoxia is mediated by various mechanisms, which involve different nicotinic cholinergic receptors. They differ from the resistance mechanisms in non-trained rats.     

Role of Cholinergic Structures in Individual Resistance of Rat Circulatory System to Posthemorrhagic Hypoxia

Experiments employing ultrasound technique showed that nonselective blockade of central muscarinic cholinoceptors with amizyl significantly increases the number and lifespan of rats highly resistant to acute massive blood loss. This pretreatment increased individual resistance of the circulatory system to posthemorrhagic hypoxia (blood pressure and portal blood flow rate). Preliminary blockade of central nicotinic cholinoceptors and peripheral muscarinic cholinoceptors with cyclodol and methacin, respectively, had no effect on the percentage of rats highly and low resistant to acute blood loss. Preliminary blockade of peripheral muscarinic cholinoceptors with methacin prevented the decrease in the cardiac output in low resistant animals during the posthemorrhagic period. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 8, pp. 142–145, August, 2005     

Effect of intermittent normobaric hypoxia on kinetic properties of mitochondrial enzymes

We studied the effect of intermittent normobaric hypoxia on the formation of adaptive signs and state of mitochondrial enzymes in the cerebral cortex of rats with different resistance to hypoxia. Kinetic parameters for mitochondrial enzymes in the substrate region of the respiratory chain of the cerebral cortex underwent various changes in low resistant and highly resistant rats over the first 2 h after 1-h intermittent normobaric hypoxia. Low resistant animals were characterized by more effective functioning of rotenone-sensitive NADH-cytochrome C reductase and succinate-cytochrome C reductase under conditions of increased reduction status of the cell. These features correlated with the increase in the general resistance of animals. Significant changes in kinetic properties of mitochondrial enzymes and signs of the development of resistance were not found in highly resistant rats. Reciprocal relations between mitochondrial enzyme complexes in the substrate region of the respiratory chain probably play a role of the signal regulatory mechanism, which mediates tissue-specific and general resistance of rats under conditions of intermittent normobaric hypoxia. These effects did not depend on oxygenation of the inhaled gas mixture during the inter-hypoxic period. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 12, pp. 644–651, December, 2007     

Changes in hypoxia resistance in rats during daytime

The resistance to acute hypoxia in male Wistar rats was evaluated by the period of survival after exposure to high-altitude hypoxia (11.5 km above see level). The study was performed during daytime (13.00–21.00) in autumn. The fatal rat population was characterized by the log-normal distribution of survival periods. The rats with low and moderate resistance to hypoxia exhibited similar diurnal variations in it with gradual decrease by the end of daytime more pronounced in low-resistant rats. The rats with high resistance showed relatively constant resistance to hypoxia which decreased only at 21:00. All groups revealed a relatively stable resistance to hypoxia from 16:00 to 18:00. These variations in the resistance to hypoxia should be taken into consideration when planning experimental research. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 3, pp. 256–260, March 1999     

Effect of lithium hydroxybutyrate on hemodynamics and respiration in rats with different resistance to hypoxia

Acute experiments on narcotized rats showed that intravenous infusion of GABA derivative lithium hydroxybutyrate induced different changes in hemodynamic and respiratory parameters in animals with high and low resistance to hypoxia. Rats highly resistant to hypoxia better tolerated lithium hydroxybutyrate treatment compared to low resistant animals. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 1, pp. 16–20, January, 2006     

低压缺氧复合NaCN中毒对大鼠呼吸频率及BALF成份的影响

目的研究低压缺氧复合氰化钠(NaCN)中毒对大鼠呼吸频率及支气管肺泡灌洗液(BALF)细胞数和总蛋白(TP)含量的影响。方法SD大鼠84只,随机分为常压常氧和低压缺氧2组。常压常氧组动物于重庆地区常规实验室内进行实验。将低压缺氧组动物置低压舱61 kPa环境放置72 h后开始实验。以3.6 mg/kg氰化钠皮下注射染毒,用RM6240型多道生理信号采集处理系统记录呼吸频率。制备BALF,测定BALF中细胞数,Lowery法测TP含量。结果低压缺氧致动物呼吸频率加快,但无统计学意义。BALF中细胞数和TP含量显著升高。低压缺氧动物NaCN中毒后呼吸频率及BALF中细胞数和TP含量进一步升高,均有显著性差异。结论低压缺氧加重NaCN中毒对大鼠呼吸系统的损伤作用。     

Parameters of Adenylate Pool as Predictors of Energy Metabolism Disturbances in Hepatocytes during Hypoxia

We studied the dependence of various parameters of adenylate pool in hepatocytes on oxygen concentrations. Isolated cells responded to a decrease in oxygen content in their microenvironment by changes in components of the adenine nucleotide system, which attested to phasic nature of this process. Three ranges of oxygen concentrations differing by the type of changes in the parameters of adenylate pool were distinguished: steady-state range of these parameters; primary changes in the adenylate pool aimed at minimization of energy losses (compensatory stage characteristic of the initial stages of hypoxia); and linear drop of ATP content paralleled by decompensation of the regulatory mechanisms of ATP formation and adenine nucleotide degradation. Hence, parameters of the adenylate pool can serve as predictors of different stages of hypoxia. Differences in the parameters of adenylate pool depending on the level of O₂ in hepatocytes of rats highly and low-resistant to hypoxia indicate that energy metabolism is a mechanism involved in the formation of individual cell resistance to oxygen deficiency. These data suggest that suspension of isolated hepatocytes as an adequate cellular model for experimental studies of the effects of hypoxia on energy metabolism and functional activity of the cell.     

Morphological Changes in Myocardium in Rats with Different Resistance to Hypoxia after Ligation of the Coronary Artery

We studied morphological changes in the myocardium during experimental myocardial infarction in rats with different resistance to hypoxia. Microscopic examination showed that morphological changes in the ischemic zone and adjacent tissues are different in rats with high and low resistance to acute ischemia. In highly resistant rats, necrotic changes in cardiomyocytes included focal contracture and loosening. These changes were followed by the formation of focal necroses with well-defined boundaries, dense demarcation infiltrates, and pronounced hypertrophy of cardiomyocytes in the adjacent tissue. In low resistant rats, pronounced edema in the ischemia zone and numerous hemorrhages in the interstitial tissue developed in the early stage after coronary occlusion. These changes were followed by the formation of more extensive necrotic areas with diffuse boundaries, less pronounced demarcation, and irregular hypertrophy of cardiomyocytes in the surrounding tissue.     

Effects of adaptation to periodic hypoxia on kinetic parameters of respiratory chain enzymes in rat brain

A study of kinetic parameters of brain respiratory enzymes revealed that the maximal velocity and the Michaelis apparent constant for NADH-cytochrome C-reductase are significantly lower in low-resistant rats than in rats with a high resistance to hypoxia. Adaptation to periodic hypoxia increases total resistance only in low-resistant rats. It is accompanied by an increase in the values of kinetics parameters for NADH-cytochrome C-reductase and cytochrome oxidase. Kinetic parameters for these enzymes in the brain of high-resistant rats are either unaltered or even decreased. It is suggested that the first enzymatic complex of the respiratory chain is one of the limiting or regulating links in energy metabolism determining the brain's resistance to hypoxia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 3, pp. 252–255, March, 1996.